Preservation of neurological function following therapeutic hypothermia in a patient of in-hospital cardiac arrest with non-ventricular fibrillation

Summary

A 76-year-old woman with a diagnosis of dilated-phase hypertrophic cardiomyopathy was admitted to our hospital for exacerbation of congestive heart failure. After admission, she developed cardiac arrest and the electrocardiogram showed pulseless electrical activity. Cardiopulmonary resuscitation was started immediately; however, return of spontaneous circulation was achieved 56 min after cardiopulmonary arrest. Therapeutic hypothermia was considered as an adjunct therapy, together with intensive treatment. The target temperature of 33.0 °C was achieved 10 h after cardiopulmonary arrest. Core temperature was maintained between 33.0 and 35.0 °C for 72 h with no cardiac arrhythmia detected during this period. Re-warming was initiated at a rate of 1 °C/day. On day 6, the core temperature returned to 37 °C and recovery of consciousness was achieved on day 9. No impairment of neurological function was noted. She had no heart failure-related symptoms and B-type natriuretic peptide level decreased from 4174 pg/mL on admission to 450 pg/mL at discharge. Therapeutic hypothermia may be a promising post-resuscitation therapy for comatose survivors of in-hospital cardiac arrest with non-ventricular fibrillation leading to improvement in neurological outcome.

Introduction

Recent reports have demonstrated that paramedics carry out electrical cardioversion by automated external defibrillator and that successful defibrillation can be achieved outside the hospital [1]. The 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend mild therapeutic hypothermia for patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest [2]. However, the initial cardiac rhythm of comatose patients is limited to ventricular fibrillation (VF).

We present a patient who developed in-hospital cardiac arrest with non-VF rhythm and achieved ROSC after 1-h standard cardiopulmonary resuscitation (CPR). Therapeutic hypothermia over 6 days, in combination with a series of therapeutic interventions, resulted in full recovery without any neurological deficits.

Case report

A 76-year-old woman was diagnosed with hypertrophic cardiomyopathy and atrial fibrillation 14 years prior to the present admission. Her mother and elder sister were also known to have hypertrophic cardiomyopathy. She was treated chiefly with diuretics and warfarin in the outpatient clinic. Transthoracic echocardiogram showed low left ventricular (LV) ejection fraction, LV dilatation, and progressive LV wall thinning in recent years. Based on these findings, the disease stage was considered the dilated phase of hypertrophic cardiomyopathy.

She developed dyspnea associated with congestive heart failure and was treated by intravenous diuretics by the family physician. However, urinary output was limited and systolic blood pressure was 70 mmHg. The symptoms of heart failure deteriorated and she was transferred to the emergency room in our hospital by an ambulance. On admission, blood pressure was 100/70 mmHg and heart rate was 60 beats/min under infusion of dopamine 3γ. Arterial oxygen saturation was 90% during oxygen breathing at 3 L/min through a nasal cannula. The electrocardiogram (ECG) showed sinus rhythm with complete right bundle branch block (Fig. 1) and transthoracic echocardiogram showed LV dilatation and severe diffuse hypokinesis (LV end-diastolic diameter: 69 mm; LV ejection fraction: 20%). During clinical examination, she developed rapid fall in heart rate and hypotension, with imminent cardiogenic shock and she was quickly taken to the cardiac catheterization room. Within minutes, she developed cardiopulmonary arrest and the ECG monitor showed pulseless electrical activity (PEA). According to the protocol of advanced cardiovascular life support, CPR was started immediately together with tracheal intubation, but spontaneous circulation did not resume immediately. ROSC was achieved exactly 56 min after cardiopulmonary arrest, during which a temporary pacing lead, an aortic balloon for intra-aortic balloon pumping, and a central venous catheter were inserted. The patient was subsequently transferred to the intensive care unit (ICU) for close monitoring and treatment.

Figure 1.

Electrocardiogram on hospital admission.

In the ICU, the Glasgow Coma Scale was E₁V₁M₁. Both pupils were dilated (∅ 5 mm) and the light reflex was absent. Body temperature was 36.2 °C as measured by a probe inserted into the bladder. A plain chest X-ray showed cardiomegaly and pulmonary congestion (Fig. 2). The laboratory tests were performed. Serum creatinine (1.81 mg/dL) and creatine phosphokinase levels (1113 U/L) were increased and the level of B-type natriuretic peptide (BNP) was 4174 pg/mL; however, serum troponin T level was normal (0.03 ng/mL).

Figure 2.

Chest X-ray on hospital admission.

Therapeutic hypothermia was considered as a curative option for this patient (Fig. 3). Mild to moderate hypothermia was maintained with a water blanket and was combined with continuous hemodiafiltration to treat the associated acute renal failure. The patient was sedated with propofol and fentanyl, and treated with vecuronium bromide to prevent shivering. The target body temperature of 33.0 °C was achieved 10 h after cardiopulmonary arrest. The core temperature was maintained between 33.0 and 35.0 °C for 72 h and no arrhythmia was detected during this period. Re-warming was initiated at a rate of 1 °C/day. During the re-warming phase, atrial fibrillation with tachycardia often occurred, necessitating intravenous infusion of procainamide as well as cardioversion.

Figure 3.

Clinical course. CHDF, continuous hemodiafiltration; DOA, dopamine; DOB, dobutamine; dPAP, diastolic pulmonary arterial pressure; hANP, human atrial natriuretic peptide; IABP, intra-aortic balloon pumping; LVDd, left ventricular diastolic diameter; LVEF, left ventricular ejection fraction; NA, noradrenaline; d/sPAP, diastolic/systolic pulmonary arterial pressure.

On day 6, the core temperature returned to 37 °C, thus ending the period of therapeutic hypothermia. At that stage, the intra-aortic balloon pump was removed and the doses of inotropic agents were increased on day 7. On day 8, infusion of the sedative drug was discontinued, the patient was extubated, and she finally regained consciousness (Glasgow come scale: E₃V₅M₆) on day 9. On day 12, infusion of inotropic agents was gradually decreased and treatment with oral angiotensin-converting enzyme inhibitor, β-blocker, and amiodarone was initiated. At that stage, detailed neurological examination showed no functional deficits. She had no heart failure-related symptoms and the BNP level decreased to 450 pg/mL on hospital discharge. The LV end-diastolic dimension at discharge (69 mm) was comparable to that on admission, however LV ejection fraction increased from 20% on admission to 44% at discharge. A close follow-up at the outpatient clinic over the 2 years after discharge showed no recurrence of heart failure.

Discussion

Therapeutic hypothermia is recommended for patients with ROSC after out-of-hospital cardiac arrest due to VF and has been reported to improve survival and neurological function [2], [3]. One study documented improved metabolic endpoints (lactate and O₂ extraction) when comatose patients were cooled after ROSC from out-of-hospital cardiac arrest in which the initial rhythm was PEA/asystole [4]. A small study also reported benefits after therapeutic hypothermia in comatose survivors of non-VF arrest [5]. On the other hand, few studies have reported the benefits for patients with in-hospital cardiac arrest. The largest published in-hospital cardiac arrest database by the National Registry of Cardiopulmonary Resuscitation Investigators indicates that pulseless arrest rhythm in adults is typically PEA/asystole associated with preexisting conditions, such as progressive respiratory failure, circulatory shock, or both, compared with VF or pulseless ventricular tachycardia [6]. Furthermore, the reported survival rate to hospital discharge following PEA/asystole is only 11% [6].

The ultimate goal of resuscitation in patients with in-hospital cardiac arrest is survival to hospital discharge with good neurological outcome. Interventions likely to improve survival include early recognition, faster and better resuscitation, and stabilization of such patients. The present case developed PEA associated with congestive heart failure and deterioration of LV function. About 1 h passed until the achievement of ROSC although CPR was initiated immediately after cardiac arrest. The reason for the effectiveness of therapeutic hypothermia in this case could not be elucidated. It is questionable whether therapeutic hypothermia is suitable for patients having severe cardiac dysfunction because drastic changes of body temperature may cause arrhythmia, leading to hemodynamic deterioration. Therefore, a gentle protocol on temperature regulation was adopted. Actually, atrial fibrillation with tachycardia often occurred during the re-warming phase and we had trouble ceasing a surge of arrhythmia in this case. This case may be appropriate for percutaneous cardiopulmonary support (PCPS), but she was a person of advanced age and her hemodynamics could be supported by intra-aortic balloon pumping alone after successful resuscitation. The PCPS has not been managed in the clinical course although we thought about the use of PCPS in this case. However, we actively induced therapeutic hypothermia in addition to mechanical support and aggressive treatment in the hope of improvement of survival and preservation of neurological function.

The indication of therapeutic hypothermia is limited according to the 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care [2]. Further evaluation in a large number of patients is required to confirm the beneficial effects of hypothermia in patients who develop in-hospital cardiac arrest with non-VF rhythms and have preexisting severe conditions. Therapeutic hypothermia may be a promising post-resuscitation therapy for comatose survivors of in-hospital cardiac arrest, leading to improvement of survival with minimal or no neurological deficits.